There is convincing evidence that polyamines are intimately linked to the growth of mammalian cells and that many changes in cellular metabolism induced by hormones (such as growth hormone, glucagon, corticosteroids and sex hormones) and other agents are accompanied by marked increases in the rate of synthesis of putrescine and spermidine brought about by increases in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase. The proposed experiments will extend knowledge of these enzymes (which have interesting regulatory properties and very rapid apparent rates of synthesis and degradation) and of other enzymes involved in polyamine metabolism. A more detailed understanding of the levels of polyamines and derivatives in cells in various physiological states and of the metabolic reactions undergone by polyamines which should result from these studies will aid in the determination of the biological function of these compounds. In addition, these studies may define the basis for enhanced excretion in tumor-bearing animals and human patients. The properties and biosynthesis and degradation of S-adenosylmethionine decarboxylase will be investigated following purification of the enzyme by affinity chromatography on columns of methylglyoxal bis (guanylhydrazone) bound to Sepharose. The nature of the enzyme cofactor, the mechanism by which putrescine stimulates activity and by which methylglyoxal bis (guanylhydrazone) derivatives inhibit decarboxylation and reduce the apparent rate of degradation of the enzyme will be studied. Similar studies of the induction and turn-over of ornithine decarboxylase will be made. Levels of polyamines and derivatives and effects of inhibitors of polyamine synthesis will be studied in cultured liver cells and lymphocytes. The formation of acetyl-derivatives of putrescine and polyamines, the possible occurrence of glutathionyl complexes of polyamines and the mechanism of the conversion of spermidine into putrescine in rat liver cells after administration of hepatotoxic and carcinogenic agents will be investigated.